Analysis of candidate genes for macular telangiectasia type 2

Nancy L Parmalee, Carl Schubert, Joanna E Merriam, Kaija Allikmets, Alan C Bird, Mark C Gillies, Tunde Peto, Maria Figueroa, Martin Friedlander, Marcus Fruttiger, John Greenwood, Stephen E Moss, Lois E H Smith, Carmel Toomes, Chris F Inglehearn, Rando Allikmets

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


PURPOSE: To find the gene(s) responsible for macular telangiectasia type 2 (MacTel) by a candidate-gene screening approach.

METHODS: Candidate genes were selected based on the following criteria: those known to cause or be associated with diseases with phenotypes similar to MacTel, genes with known function in the retinal vasculature or macular pigment transport, genes that emerged from expression microarray data from mouse models designed to mimic MacTel phenotype characteristics, and genes expressed in the retina that are also related to diabetes or hypertension, which have increased prevalence in MacTel patients. Probands from eight families with at least two affected individuals were screened by direct sequencing of 27 candidate genes. Identified nonsynonymous variants were analyzed to determine whether they co-segregate with the disease in families. Allele frequencies were determined by TaqMan analysis of the large MacTel and control cohorts.

RESULTS: We identified 23 nonsynonymous variants in 27 candidate genes in at least one proband. Of these, eight were known single nucleotide polymorphisms (SNPs) with allele frequencies of >0.05; these variants were excluded from further analyses. Three previously unidentified missense variants, three missense variants with reported disease association, and five rare variants were analyzed for segregation and/or allele frequencies. No variant fulfilled the criteria of being causal for MacTel. A missense mutation, p.Pro33Ser in frizzled homolog (Drosophila) 4 (FZD4), previously suggested as a disease-causing variant in familial exudative vitreoretinopathy, was determined to be a rare benign polymorphism.

CONCLUSIONS: We have ruled out the exons and flanking intronic regions in 27 candidate genes as harboring causal mutations for MacTel.

Original languageEnglish
Pages (from-to)2718-26
Number of pages9
JournalMolecular Vision
Publication statusPublished - 14 Dec 2010


  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biological Transport
  • Chromosome Segregation
  • DNA Mutational Analysis
  • Female
  • Gene Expression Profiling
  • Genetic Linkage
  • Humans
  • Macula Lutea
  • Male
  • Mice
  • Middle Aged
  • Neovascularization, Pathologic
  • Oligonucleotide Array Sequence Analysis
  • Pedigree
  • Phenotype
  • Retinal Pigments
  • Telangiectasis
  • Journal Article
  • Research Support, Non-U.S. Gov't


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